C/EBPα mediates UVA-induced MMP1 overexpression in a histone H3 acetylation-dependent manner during skin photoaging.

UVA-induced skin photoaging mechanisms involve inflammation and dysregulation of matrix metalloproteinase (MMP) expression. In UVA-induced photoaging, MMP1 expression is increased in dermal fibroblasts, thereby facilitating skin damage and degradation of extracellular matrix (ECM) components, such as type I collagen. To investigate whether UVA influences the level of histone H3 acetylation of the MMP1 promoter via C/EBPα/P300. In this study, skin samples (from both exposed and unexposed areas) were collected from 10 subjects, and a fibroblast photoaging model was concurrently established. RT-qPCR, western blotting, and ChIP-qPCR were employed to assess C/EBPα, P300, MMP1, and COL1A1 expression levels in the dermis and primary fibroblasts. Additionally, ChIP-qPCR was utilized to validate the binding of C/EBPα to the MMP1 promoter region, while co-immunoprecipitation was performed to confirm interaction between C/EBPα and P300. ChIP-qPCR was employed to examine the level of binding of relevant genes to the MMP1 promoter after exposure to light. Transfection with overexpression plasmids and siRNA targeting C/EBPα and P300 was performed, followed by RT-qPCR, western blotting, and ChIP-qPCR, to ascertain whether the regulation of MMP1 by C/EBPα is dependent on P300. We observed increased MMP1 mRNA and protein levels in UVA-exposed samples, which significantly positively correlated with histone H3 acetylation of the MMP1 promoter. This phenomenon may be related to UVA-induced C/EBPα-P300 complex formation, mediated by histone acetylation of the MMP1 promoter. Our findings reveal that UVA-induced upregulation of MMP1 expression, mediated by C/EBPα, is partially dependent on acetylation, and that this mechanism might be a potential therapeutic target for photoaging.